Publications by authors named "Giulio Andrea Bertani"

9 Publications

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Does COVID-19 Affect Survival and Functional Outcome in Emergency and Urgent Neurosurgical Procedures? A Single-Center Prospective Experience During the Pandemic.

World Neurosurg 2021 Jun 22. Epub 2021 Jun 22.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Milan, Italy; "Aldo Ravelli" Research Center, Milan, Italy.

Objective: To assess organizational and technical difficulties of neurosurgical procedures during the coronavirus disease 2019 (COVID-19) pandemic and their possible impact on survival and functional outcome and to evaluate virological exposure risk of medical personnel.

Methods: Data for all urgent surgical procedures performed in the COVID-19 operating room were prospectively collected. Preoperative and postoperative variables included demographics, pathology, Karnofsky performance status (KPS) and neurological status at admission, type and duration of surgical procedures, length of stay, postoperative KPS and functional outcome comparison, and destination at discharge. We defined 5 classes of pathologies (traumatic, oncological, vascular, infection, hydrocephalus) and 4 surgical categories (burr hole, craniotomy, cerebrospinal fluid shunting, spine surgery). Postoperative SARS-CoV-2 infection was checked in all the operators.

Results: We identified 11 traumatic cases (44%), 4 infections (16%), 6 vascular events (24%), 2 hydrocephalus conditions (8%), and 2 oncological cases (8%). Surgical procedures included 11 burr holes (44%), 7 craniotomies (28%), 6 cerebrospinal fluid shunts (24%), and 1 spine surgery (4%). Mean patient age was 57.8 years. The most frequent clinical presentation was coma (44 cases). Mean KPS score at admission was 20 ± 10, mean surgery duration was 85 ± 63 minutes, and mean length of stay was 27 ± 12 days. Mean KPS score at discharge was 35 ± 25. Outcome comparison showed improvement in 16 patients. Four patients died. Mean follow-up was 6 ± 3 months. None of the operators developed postoperative SARS-CoV-2 infection.

Conclusions: Standardized protocols are mandatory to guarantee a high standard of care for emergency and urgent surgeries during the COVID-19 pandemic. Personal protective equipment affects maneuverability, dexterity, and duration of interventions without affecting survival and functional outcome.
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http://dx.doi.org/10.1016/j.wneu.2021.06.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216838PMC
June 2021

The "Parachute" Technique for the Endoscopic Repair of High-Flow Anterior Skull-Base CSF Leaks.

World Neurosurg 2021 Jul 8;151:e880-e887. Epub 2021 May 8.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; "Aldo Ravelli" Research Center, Milan, Italy; Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Milan, Italy.

Objective: This study aims to assess the feasibility and reliability of our endoscopic trans-nasal technique for the repair of cribriform and sellar high-flow cerebrospinal fluid (CSF) leaks.

Methods: A comparison between patients suffering from high-flow rhinorrhea and treated through a free grafting endoscopic technique or the "parachute" technique, our nasal packing proposal, was performed.

Results: Thirty-three patients were included. The mean age was 52 years (range: 36-68 years). The etiology of the CSF leaks was iatrogenic in 16 cases (48.5%), traumatic in 5 cases (15.2%), spontaneous in 11 cases (33.3%), and related to anterior skull base tumors in 1 case (3%). The bone defect affected the sphenoidal sinus in 20 cases (60.6%), the cribriform plate of the ethmoid in 10 cases (30.3%), and both the sphenoid and ethmoid in 3 cases (9.1%). The mean size of bone defects was 8.5 ± 3.9 mm. The median follow-up was 28 (64) months. A CSF leak recurrence occurred in no cases treated with the parachute technique and in 3 cases that underwent conventional endoscopic treatments. The CSF leak recurrences were associated with 2 iatrogenic and 1 post-traumatic fistula. All the CSF leak recurrences underwent the parachute technique, not showing second recurrences.

Conclusions: Our results suggest that the parachute technique is simple, safe, and effective. We recommend it as an alternative treatment to vascular flaps for the treatment of high-flow and recurrent fistulas.
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http://dx.doi.org/10.1016/j.wneu.2021.05.006DOI Listing
July 2021

Insular lobe surgery and cognitive impairment in gliomas operated with intraoperative neurophysiological monitoring.

Acta Neurochir (Wien) 2021 05 24;163(5):1279-1289. Epub 2020 Nov 24.

Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Padiglione Monteggia, 20122, Milan, Italy.

Background: For a long time, surgery of insular gliomas was considered at high risk for postoperative cognitive deficits, but recent studies highlighted the feasibility of the surgical approach. The aims of our study were to investigate the presence of language impairment before and after surgery and the relationship between language impairment and tumor volume preoperatively and extent of resection (EOR) 3 months after surgery.

Methods: Thirty-five patients with insular gliomas underwent an extensive language assessment before and few days after surgery, and after 3 months. Intraoperative neurophysiological monitoring (IOM) and brain mapping with direct electrical stimulation (DES) were used in all the cases; 8 patients underwent awake craniotomy. Statistical analysis was performed on the language tests administered.

Results: Patients with pure left insular lesion showed language impairment before and after surgery. Overall, patients with a left lesion showed a drop of performance after surgery followed by a partial recovery. Moreover, when the tumor involved the insula and adjacent networks, we observed a more severe deficit. No correlations were found between tumor volume, EOR, and language impairment.

Conclusions: Left insular lobe is an important hub in language networks; its involvement determines pre- and postsurgical deficits, together with the involvement of white matter connections. Tumor volume and EOR are not risk factors per se directly related to language functioning. Surgery of insular gliomas is possible with a pre- and intraoperative extensive study of the patient with IOM and awake surgery, and encouraged by the trend of cognitive recovery highlighted.
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http://dx.doi.org/10.1007/s00701-020-04643-9DOI Listing
May 2021

Propranolol for familial cerebral cavernous malformation (Treat_CCM): study protocol for a randomized controlled pilot trial.

Trials 2020 May 12;21(1):401. Epub 2020 May 12.

Laboratory of Cardiovascular Clinical Pharmacology, Mario Negri Institute for Pharmacological Research-IRCCS, Via Mario Negri, 2, 20156, Milan, Italy.

Background: Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression.

Methods: Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40-80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory).

Discussion: Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial.

Trial Registration: ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.
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http://dx.doi.org/10.1186/s13063-020-4202-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218540PMC
May 2020

Long-term follow-up of neuropsychological functions in patients with high grade gliomas: can cognitive status predict patient's outcome after surgery?

Acta Neurochir (Wien) 2020 04 28;162(4):803-812. Epub 2020 Jan 28.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35 (Padiglione Monteggia), 20122, Milan, Italy.

Background: Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12-16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery.

Methods: One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered.

Results: First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered.

Conclusion: Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.
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http://dx.doi.org/10.1007/s00701-020-04230-yDOI Listing
April 2020

Constructional Apraxia in Older Patients with Brain Tumors: Considerations with an Up-To-Date Review of the Literature.

World Neurosurg 2018 Jun 31;114:e1130-e1137. Epub 2018 Mar 31.

Division of Neurosurgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Background: Constructional apraxia (CA) is a neuropsychological impairment of either basic perceptual and motor abilities or executive functions, in the absence of any kind of motor or perceptual deficit. Considering patients with focal brain tumors, CA is common in left or right parietal and parieto-occipital lesions. In neuropsychology, the Rey-Osterrieth Complex Figure Test (ROCFT; or parallel forms) is commonly used for the assessment of CA. This study stems from a clinical observation of a difficulty with CA tests for the majority of older neurosurgical patients without occipitoparietal lesions.

Methods: Patients were tested at 3 points: before surgery, 3 months after surgery, and 12 months after surgery. Thirty patients (15 meningiomas and 15 glioblastomas) were studied retrospectively.

Results: Older patients with focal brain lesions, regardless of the nature of the tumor, performed poorly at CA tests. More than 50% of patients obtained pathologic results at all 3 times considered.

Conclusions: Our findings suggest that as CA complex tests involve multiple domains, poor results in copy task may reflect a global cognitive deficit of older patients with tumors, without a specific constructional praxis deficit. CA complex tests (such as the ROCFT) do not give significant informations about visuo-constructional abilities.
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http://dx.doi.org/10.1016/j.wneu.2018.03.159DOI Listing
June 2018

Long-Standing Isolated Autoimmune Hypothalamitis Diagnosed with Endoscopic Transventricular Biopsy.

World Neurosurg 2017 Sep 16;105:1036.e5-1036.e9. Epub 2017 Jun 16.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: Autoimmune hypothalamitis, which is among the causes of acquired central diabetes insipidus, has seldom been described in the literature. This condition is probably provoked by the production of anti-vasopressin-secreting cell antibodies and antihypothalamus antibodies and is often associated with pituitary or polyendocrine autoimmunity. Correct diagnosis and immediate treatment are essential to avoid the progression of the pathologic process.

Case Description: A woman diagnosed with central diabetes insipidus 12 years ago, who had panhypopituitarism and mild memory deficit, came to our attention. She refused radiologic studies. Magnetic resonance imaging performed in our unit showed a contrast-enhancing hypothalamic lesion. Lumbar puncture was negative for neoplastic markers. We decided to perform a biopsy of the lesion to obtain a histopathologic examination of the tissue and chose an endoscopic transventricular approach to reach the floor of the third ventricle. Autoimmune hypothalamitis was diagnosed and treatment with steroids and azathioprine was started. The lesion size decreased and was stable after 17 months of follow-up.

Conclusions: The endoscopic transventricular approach has proved to be an effective and safe way to obtain tissue samples for histopathologic examination from a region that is usually difficult to reach; it also gives direct visualization of the lesion, which makes sampling easier. The lesion size decreased after treatment but no clinical improvement was detected, either on the cognitive or on the endocrinologic side.
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http://dx.doi.org/10.1016/j.wneu.2017.06.055DOI Listing
September 2017

Endothelial Cells Lining Sporadic Cerebral Cavernous Malformation Cavernomas Undergo Endothelial-to-Mesenchymal Transition.

Stroke 2016 Mar 2;47(3):886-90. Epub 2016 Feb 2.

From the New Strategies to Inhibit Tumor Angiogenesis Program Fondazione Italiana per la Ricerca sul Cancro (FIRC) Institute of Molecular Oncology Fondazione, Milan, Italy (L.B., M.M., F.P., N.R., R.C., E.D., M.G.L.); Institute of Neurosurgery (R.P.) and Department of Pathology (M.M., L.M.L.), Università Cattolica Sacro Cuore, Roma; Department of Surgery Division of Neurosurgery, U.O. Neurochirurgia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milano (M.L., V.L., G.A.B.); Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (E.D.); and Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research, Milan, Italy (M.G.L.).

Background And Purpose: Cerebral cavernous malformation (CCM) is characterized by multiple lumen vascular malformations in the central nervous system that can cause neurological symptoms and brain hemorrhages. About 20% of CCM patients have an inherited form of the disease with ubiquitous loss-of-function mutation in any one of 3 genes CCM1, CCM2, and CCM3. The rest of patients develop sporadic vascular lesions histologically similar to those of the inherited form and likely mediated by a biallelic acquired mutation of CCM genes in the brain vasculature. However, the molecular phenotypic features of endothelial cells in CCM lesions in sporadic patients are still poorly described. This information is crucial for a targeted therapy.

Methods: We used immunofluorescence microscopy and immunohistochemistry to analyze the expression of endothelial-to-mesenchymal transition markers in the cavernoma of sporadic CCM patients in parallel with human familial cavernoma as a reference control.

Results: We report here that endothelial cells, a cell type critically involved in CCM development, undergo endothelial-to-mesenchymal transition in the lesions of sporadic patients. This switch in endothelial phenotype has been described only in genetic CCM patients and in murine models of the disease. In addition, TGF-β/p-Smad- and β-catenin-dependent signaling pathways seem activated in sporadic cavernomas as in familial ones.

Conclusions: Our findings support the use of common therapeutic strategies for both sporadic and genetic CCM malformations.
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http://dx.doi.org/10.1161/STROKEAHA.115.011867DOI Listing
March 2016

Bilateral Parkinsonism: when to image?

Pract Neurol 2015 Aug 21;15(4):300-1. Epub 2015 Apr 21.

Department of Surgery Division of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

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http://dx.doi.org/10.1136/practneurol-2015-001083DOI Listing
August 2015